The question of how noncoding RNAs are involved in Polycomb group (PcG) and Trithorax group (TrxG) regulation has been on an extraordinary journey over the last three decades. Favored models have risen and fallen, and healthy debates have swept back and forth. The field has recently reached a critical mass of compelling data that throws light on several previously unresolved issues. The time is ripe for a fruitful combination of these findings with two other long-running avenues of research, namely the biochemical properties of the PcG/TrxG system and the application of theoretical mathematical models toward an understanding of the system's regulatory properties. I propose that integrating our current knowledge of noncoding RNA into a quantitative biochemical and theoretical framework for PcG and TrxG regulation has the potential to reconcile several apparently conflicting models and identifies fascinating questions for future research.


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